MONTREAL, April 2, 2015 /PRNewswire/ -- Clementia Pharmaceuticals, Inc. announced today that the Data Monitoring Committee (DMC) for the company's Phase 2 adaptive-design, dose-ranging study of palovarotene for fibrodysplasia ossificans progressiva (FOP) has completed a planned review of efficacy and safety data from the first cohort of patients in the study. Based on the review, the committee determined that there were no safety concerns and recommended that the trial continue as designed. The second part of the study (Cohort 2) will evaluate two dosing regimens of palovarotene, and placebo, in patients with FOP.
FOP is a rare, severely disabling genetic disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) and new abnormal bone formation. This process, known as heterotopic ossification (HO), occurs in muscles, tendons and ligaments, causing significant morbidities and progressive disability.
"The DMC's review supports continuation of our Phase 2 study, with further evaluation of the Cohort 1 dose, as well as a lower dose," said Clarissa Desjardins, Ph.D., Chief Executive Officer of Clementia. "It is an important milestone in our efforts to make palovarotene available to patients with FOP, for whom there are no currently approved treatments."
The committee, a panel of experts appointed to monitor the trial, initiated its review of the data after the eighth patient in Cohort 1 completed the six-week treatment period. Based on the DMC's recommendation, enrollment of the 16 patients in Cohort 2 will begin immediately, and is expected to be complete by December 2015.
"Clementia worked closely with investigators, regulators and the patient community on the adaptive design of this Phase 2 trial. This is an innovative approach for evaluating the safety and efficacy of different doses of palovarotene as efficiently as possible," said Donna Grogan, M.D., Chief Medical Officer of Clementia. "The Cohort 1 dose of 10 mg once daily for 14 days, followed by 5 mg once daily for 28 days, was selected based on results from studies in animal models, as well as the palovarotene safety profile. The additional dose of 5 mg once daily for 14 days, followed by 2.5 mg for 28 days, to be evaluated in the second cohort, will provide valuable information regarding the effect of lower doses of palovarotene in patients with FOP."
The U.S. Food and Drug Administration (FDA) defines an adaptive-designed clinical trial as a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data from subjects in the study. The double-blind, placebo-controlled Phase 2 clinical trial is evaluating the effect of different doses of palovarotene on new bone formation during and after a flare-up in 24 patients with FOP who are 15 years of age or older.
In the trial, treatment is initiated within seven (7) days from flare-up onset and continued for six (6) weeks with an additional six (6) weeks of follow-up. Efficacy and safety endpoints include imaging endpoints for new bone formation, clinical assessments of physical function and patient-reported outcomes. Current study sites include the University of California San Francisco (UCSF), the University of Pennsylvania in Philadelphia, and the Hopital Necker-Enfants Malades in Paris, France.
In preclinical studies, palovarotene prevented heterotopic bone formation in mouse models of FOP. The ongoing Phase 2 clinical trial was designed to determine whether these effects can be replicated in patients with FOP.
For more information and answers to frequently asked questions about the palovarotene Phase 2 trial, please visit www.clementiapharma.com.
About Fibrodysplasia Ossificans Progressiva (FOP)
FOP is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in new, abnormal bone formation in muscles, tendons and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints, leading to cumulative loss of function and disability. FOP is caused by a point mutation in the ALK2/BMP Type I receptor; the mutation results in over-activity of the receptor. Virtually all known patients have the same point mutation and have congenital malformations of the big toes at birth. FOP is thought to affect less than one individual for every million lives.
Palovarotene is a retinoic acid receptor gamma agonist in-licensed from Roche Pharmaceuticals, where it was previously evaluated in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. Palovarotene has been shown to block bone formation in a variety of mouse models of FOP and is being investigated as a potential treatment for FOP.
About Clementia Pharmaceuticals, Inc.
Clementia is a privately held, clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for people living with rare diseases. The company is advancing a novel retinoic acid receptor gamma agonist to address diseases of heterotopic ossification, including fibrodysplasia ossificans progressiva. For more information, please visit www.clementiapharma.com.
SOURCE Clementia Pharmaceuticals, Inc.